Ota Motonori, Ikeguchi Mitsunori, Kidera Akinori
Graduate School of Information Science, Nagoya University, Nagoya, Aichi 464-8601, Japan.
Graduate School of Medical Life Science, Yokohama City University, Yokohama, Kanagawa 230-0045, Japan.
Biophys Physicobiol. 2016 Nov 18;13:295-304. doi: 10.2142/biophysico.13.0_295. eCollection 2016.
Understanding how proteins fold through a vast number of unfolded states is a major subject in the study of protein folding. Herein, we present itinerary profiling as a simple method to analyze molecular dynamics trajectories, and apply this method to Trp-cage. In itinerary profiling, structural clusters included in a trajectory are represented by a bit sequence, and a number of trajectories, as well as the structural clusters, can be compared and classified. As a consequence, the structural clusters that characterize the foldability of trajectories were able to be identified. The connections between the clusters were then illustrated as a network and the structural features of the clusters were examined. We found that in the true folding funnel, Trp-cage formed a left-handed main-chain topology and the Trp6 side-chain was located at the front of the main-chain ring, even in the initial unfolded states. In contrast, in the false folding funnel of the pseudo-native states, in which the Trp6 side-chain is upside down in the protein core, Trp-cage had a right-handed main-chain topology and the Trp side-chain was at the back. The initial topological partition, as determined by the main-chain handedness and the location of the Trp residue, predetermines Trp-cage foldability and the destination of the trajectory to the native state or the pseudo-native states.
理解蛋白质如何通过大量未折叠状态进行折叠是蛋白质折叠研究中的一个主要课题。在此，我们提出行程分析作为一种分析分子动力学轨迹的简单方法，并将该方法应用于色氨酸笼。在行程分析中，轨迹中包含的结构簇由一个位序列表示，并且可以比较和分类多个轨迹以及结构簇。结果，能够识别表征轨迹可折叠性的结构簇。然后将簇之间的连接绘制成网络并检查簇的结构特征。我们发现，在真正的折叠漏斗中，即使在初始未折叠状态下，色氨酸笼也形成了左手主链拓扑结构，并且Trp6侧链位于主链环的前面。相比之下，在假天然状态的假折叠漏斗中，Trp6侧链在蛋白质核心中是颠倒的，色氨酸笼具有右手主链拓扑结构，并且Trp侧链在后面。由主链手性和Trp残基的位置确定的初始拓扑划分预先决定了色氨酸笼的可折叠性以及轨迹到达天然状态或假天然状态的目的地。
